How neurons acquire specific and unique differentiated traits in the embryonic brain, and how they use these properties to grow to specific brain centers and assemble functional synaptic connections is one of the last frontiers of biologic research. Our ignorance of these mechanisms is all the more embarrassing for our inability to reinduce specific nerve growth following brain or spinal injury in adult human patients. By means of position-dependent differentiation, young neurons acquire unique cellular properties which govern their relations with other neurons, their role and position in fiber projections, and the formation of synaptic connections. We are undertaking a comprehensive and interdisciplinary approach to major unresolved questions on the determination and development of neuronal locus specificity in retinal ganglion cells (and certain other nerves), and the expression of these properties during the assembly of retinotectal connections in frogs and fish. Our work to date has demonstrated combinatorial coding of specificity on individual optic fibers, provided minimum estimates of the number of specifiers in the retina (30x30x3), demonstrated competition among optic fibers for target sites, and begun to characterize unique informational properties in the tectum. New pilots on retinal cell layering, and on chimerae of the spastic mutant axolotl have also been initiated.